The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status

Vaitla, Pradeep; Craici, Iasmina M.; Leeaphorn, Napat; Hansrivijit, Panupong; Salim, Sohail Abdul; Rivera, Franco H Cabeza; Cheungpasitporn, Wisit

doi:10.3390/jcm9051480

Cited by 30 publications

(23 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, recent studies suggest that dd-cfDNA determination could also have a broader meaning beyond AR diagnosis, reflecting graft injury and consequently exerting a negative impact on several long-term outcomes [ 109 ]. Of interest, a multicentric study on patients with initial TCMR (TCMR 1A and borderline lesions) showed that dd-cfDNA levels above 0.5% were effective in stratifying risk of eGFR decline, de novo DSA development and further AR episodes [ 110 ].…”

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

View full text Add to dashboard Cite

New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

show abstract

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Since its discovery in 1948, cfDNA has made an impactful change in transplantation. A growing body of evidence (109 manuscripts from 55 studies) and clinical use has demonstrated that donor-derived cell-free DNA (dd-cfDNA), as an early and accurate detector of allograft injury, provides a quantitative marker of inflammation as part of screening and routine monitoring during the post-transplant period (Knight et al 2019;Sherwood and Weimer 2018;Thongprayoon et al 2020).…”

Section: Donor Derived Cell Free Dnamentioning

confidence: 99%

Understanding and using AlloSure donor derived cell-free DNA

et al. 2020

View full text Add to dashboard Cite

Renal transplant is a lifesaving and cost-effective intervention for patients with End Stage Renal Failure. Yet it is often regarded as replacement therapy rather than a cure given the overall failure rate over time. With a shortage of organs, this global issue has been further compounded by increased incidences of obesity, hypertension and diabetes, such that the disease burden and need for transplantation continues to increase. Considering the lifetime of immunosupression in transplant patients, there will also be significant associated co-morbidities By leveraging the advances in innovation in Next Generation Sequencing, the field of transplant can now monitor patients with an optimized surveillance schedule, and change the care paradigm in the post-transplant landscape. Notably, low grade inflammation is an independent risk for mortality across different disease states. In transplantation, sub-clinical inflammation enhances acute and chronic rejection, as well as accelerates pathologies that leads to graft loss. Cell free DNA has been shown to be increased in inflammatory processes as we all as provide an independent predictor of all-cause mortality. This review considers the utility of AlloSure, a donor derived cell free DNA molecular surveillance tool, which has shown new clinical insights on how best to manage renal transplant patients, and how to improve patient outcomes.

show abstract

“…Donor derived cell‐free DNA (Allosure and Prospera), a noninvasive marker of allograft injury, has also been used to determine the risk of rejection or other causes of allograft injury. The use of these less‐invasive tests has demonstrated mixed results and their true utility in solid organ transplant is still being elucidated 89 …”

Section: Future Directionsmentioning

confidence: 99%

Immunosuppression trends in solid organ transplantation: The future of individualization, monitoring, and management

2020

View full text Add to dashboard Cite

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1‐year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under‐ and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long‐term outcomes during the next era of immunosuppression, which will move from universal protocols to patient‐specific optimization.

show abstract

The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status

Cited by 30 publications

References 68 publications

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Understanding and using AlloSure donor derived cell-free DNA

Immunosuppression trends in solid organ transplantation: The future of individualization, monitoring, and management

Contact Info

Product

Resources

About